Lung cancer is the most common cause of death from cancer among men and women in the U.S.A. Recent estimates suggest that approximately 44 million persons currently smoke, and another 44 million are former smokers. Interestingly enough, more lung cancers are now being diagnosed among former smokers than current smokers. As the trend toward smoking cessation increases, lung cancers from former smokers will increase by the year 2000. Furthermore, chemopreventive strategies against current smokers have been disappointing. Thus, in addition to smoking cessation, effective chemoprevention strategies in former smokers must be developed. The overall goal of this Program Project is to develop effective chemopreventive approaches to reduce the incidence of lung cancer, especially in former smokers at high risk. To make significant progress, we have developed tightly integrated clinical and laboratory studies to create a focused, comprehensive program. This program encompasses three major directions: 1. Identify effective chemopreventive agents to prevent lung cancer. Project 1: Chemoprevention Trial in Former Smokers with 13-cis- Retinoic Acid and alpha-Tocopherol 2. Assess and quantitate mutagen sensitivity, DNA repair capacity, and genotypic characteristics that indicate a high risk for lung cancer development. Project 2: Lung Cancer Susceptibility in Former Smokers 3. Understand the fundamental biological processes of lung carcinogenesis and mechanisms of retinoid action. Project 3: Genotypic and Phenotypic Biomarkers in Lung Carcinogenesis Project 4: Mechanisms of Lung Cancer Prevention by Retinoids Core components (Administration, Biostatistics, and Data Management; and Histology) provide the structure and expertise required for the successful integration and execution of these combined clinical and laboratory studies.